Investigation and Development of a Whole-Cell Model for a Minimal Synthetic Organism

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A signicant focus in the Synthetic Biology eld has recently been investigating minimal genomes. Asof 2016, the smallest genome is that of Mycoplasma mycoides JCVI-syn3.0, which is a synthetic bacteriumderived from Mycoplasma mycoides | selected for the genome-minimisation project because it grows fast,so the turnaround of replication is ecient. Genetic material was removed from the genome accordingto a set of rules devised by the scientists, in an attempt to locate and remove all of the non-essentialgenetic material. Of the 901 mycoplasma genes, 428 were removed, but 31% of the `essential' genes haveunknown functions, so there is still work to be done in unravelling their role in the genome. Currently, alot of the minimising genome work has been trial-and-error, due to lack of knowledge about the functionof certain genes and the necessity of some genetic information, so algorithms that could analyse genomesand isolate surplus genetic material would be hugely useful in this area. This would also contributetowards simplifying whole-cell models. Bioinformatics is a useful tool that can indicate the function ofgenetic material by nding genes though data analysis | going some way to deciphering genetic code.The research that I am proposing is a continuation of the minimising genome work. Currently, thereis a working MATLAB model that simulates Mycoplasma genitalium, which consist of 28 submodelsfor di erent cell processes that are integrated together. Appropriate mathematical methods are used foreach process, such as ux-balance analysis for metabolism, and Poisson processes for protein degradation.Given the scale of the model, running and processing requires a lot of time and there are large amountsof output data. Additionally, the models are only useful for the analysis of simple organisms, but there isopportunity to develop models for other unicellular organisms; for example JCVI-syn3.0. These can beused to predict the impact that deletion of certain genes will have on the cell function, which eventuallymay indicate which genes are superfluous to the survival of the cell, and demonstrate which genes are thebasic requirements for life. Also, this can be veried in lab work, where genetic material is removed fromliving cells to see if they flourish or not. The information could then be applied to design new syntheticorganisms possessing desired functions.